1W6U

Structure of human DECR ternary complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.229 

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This is version 1.2 of the entry. See complete history


Literature

Structure and Reactivity of Human Mitochondrial 2,4-Dienoyl-Coa Reductase: Enzyme-Ligand Interactions in a Distinctive Short-Chain Reductase Active Site

Alphey, M.S.Yu, W.Byres, E.Li, D.Hunter, W.N.

(2005) J Biol Chem 280: 3068

  • DOI: https://doi.org/10.1074/jbc.M411069200
  • Primary Citation of Related Structures:  
    1W6U, 1W73, 1W8D

  • PubMed Abstract: 

    Fatty acid catabolism by beta-oxidation mainly occurs in mitochondria and to a lesser degree in peroxisomes. Poly-unsaturated fatty acids are problematic for beta-oxidation, because the enzymes directly involved are unable to process all the different double bond conformations and combinations that occur naturally. In mammals, three accessory proteins circumvent this problem by catalyzing specific isomerization and reduction reactions. Central to this process is the NADPH-dependent 2,4-dienoyl-CoA reductase. We present high resolution crystal structures of human mitochondrial 2,4-dienoyl-CoA reductase in binary complex with cofactor, and the ternary complex with NADP(+) and substrate trans-2,trans-4-dienoyl-CoA at 2.1 and 1.75 A resolution, respectively. The enzyme, a homotetramer, is a short-chain dehydrogenase/reductase with a distinctive catalytic center. Close structural similarity between the binary and ternary complexes suggests an absence of large conformational changes during binding and processing of substrate. The site of catalysis is relatively open and placed beside a flexible loop thereby allowing the enzyme to accommodate and process a wide range of fatty acids. Seven single mutants were constructed, by site-directed mutagenesis, to investigate the function of selected residues in the active site thought likely to either contribute to the architecture of the active site or to catalysis. The mutant proteins were overexpressed, purified to homogeneity, and then characterized. The structural and kinetic data are consistent and support a mechanism that derives one reducing equivalent from the cofactor, and one from solvent. Key to the acquisition of a solvent-derived proton is the orientation of substrate and stabilization of a dienolate intermediate by Tyr-199, Asn-148, and the oxidized nicotinamide.


  • Organizational Affiliation

    Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
2,4-DIENOYL-COA REDUCTASE, MITOCHONDRIAL PRECURSOR
A, B, C, D
302Homo sapiensMutation(s): 0 
EC: 1.3.1.34
UniProt & NIH Common Fund Data Resources
Find proteins for Q16698 (Homo sapiens)
Explore Q16698 
Go to UniProtKB:  Q16698
PHAROS:  Q16698
GTEx:  ENSG00000104325 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16698
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.229 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.281α = 90
b = 131.658β = 92.64
c = 70.849γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-10-28
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance